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Protein phosphorylation is critical for regulation in eukaryotic cells. The human genome encodes more than 500 protein kinases, making this one of the largest gene families. Although very diverse in how they receive and transmit signals, all protein kinases share a conserved catalytic core. While it is essential to understand how these enzymes function as catalysts, it is equally important to understand how they are regulated, how they function as scaffolds, and how they are localized.